T cell activation requires at least two independent signals. The first is mediated through recognition of MHC-peptide complexes by the T cell receptor. The second is mediated by a class of receptor-ligand pairs expressed on the cell surface of T cell and antigen presenting cells. The exact nature of these costimulatory molecules are not fully understood, although a number of candidate molecules have been proposed. Although it is possible that these putative costimulatory molecules are completely redundant, it is more likely that they are selective in their ability to costimulate different T cell subsets or activation states or during different events in T cell development. Stimulation of T cells in the absence of costimulation result sin the induction of long lived state nonresponsiveness, termed anergy. IL-production is a very sensitive readout of these events, as IL-2 is not produced in the absence of costimulation or by normal stimulation of anergized cells. The goal of these studies is to determine the molecular basis of IL-2 gene expression that is regulated during T cell activation, anergy induction, and restimulation of anergized cells. We hope to identify the key regulatory event that effects IL-2 gene expression, to determine whether other genes (less obvious to assay) are also effected, and to identify the specific factor that is induced that controls the maintenance of anergy. This will be accomplished through three specific aims: 1. Determine the role of costimulation in the regulation of the IL-2 gene in Th1 cells during T cell activation; 2. Determine whether the IL-2 gene is regulated equivalently in all T cell subsets; and 3. Determine the mechanism that suppresses IL-2 gene expression in anergized cells.